The evening of November 9th, 1938, began with typical fall solemnity for many Jews living across Germany: closing up their shops and businesses, returning home from school, and preparing family suppers. It would end with terror, as mobs ransacked storefronts, assaulted Jews on the street, and set fire to their homes. That terrible night would be known to history by the glittering debris of shattered windows lining the streets: “Kristallnacht.”

Kristallnacht, and the subsequent atrocities of Germany’s holocaust against the Jews, changed the world. Modernity had to forever acknowledge a surprising and abhorrent crime. Societies would undergo lasting changes, attempting to prevent such crimes, and the victims themselves, sadly, would suffer long-lasting impacts to their psyche.

Decades later, at the Icahn School of Medicine in New York city, Dr. Rachel Yahuda and her colleagues are working to understand just how deeply and long-lasting those consequences run. It was quickly apparent to the medical and scientific communities that holocaust survivors suffered what is now known as post-traumatic stress disorder (PTSD), plagued by symptoms of anxiety and depression into adulthood. Surprisingly, later research showed that even their children were more likely to suffer PTSD.

Dr. Yahuda thought that the burgeoning field of epigenetics might shed light on these effects. Epigenetics studies how our cells make changes to the genetic code that we all inherent from our parents. Our genes, encoded in DNA, are instructions for making proteins, the tools used by our cells to perform their jobs. All of our cells have the same DNA and will therefore have the same genes for our whole life. The work of a cell requires specialization — eye cells need to collect light, and heart cells need flex rhythmically — and they need to adapt across time — young cells need to grow, and mature cells need to respond to damage. To adapt in these ways, cells need different tools, which often means adapting their genetic code. To execute these adaptations, a cell can attach specific chemicals to its DNA, chemicals that speed up or slow down the processes of reading the code and making proteins. For example, say a brain cell needs to grow a new connection with its neighbor, it will need to produce new skeletal proteins that scaffold that growth. To do so, it can attach chemicals to the skeletal protein geneA sequence of nucleic acids that forms a unit of genetic inh... More that speed up production.

Could trauma leave lasting changes to our genetic code? Could those changes somehow be transmitted to our children?

To address these questions, Dr. Yahuda examined blood samples from holocaust survivors and their children, comparing them to similarly aged Jews who had not suffered through the holocaust, living outside of Germany at the time. They focused on a gene, FKBP5, which regulates the brain’s response to stress, and scanned that gene for the presence of a specific change to the genetic code, methylation. Methylation, or adding methyl to the DNA, is a common modification which reduces a gene’s expression into proteins.

Remarkably, a lifetime after the trauma, victims, and even their children, bore marks on their DNA. The researchers found that methylation was greater in holocaust survivors than the controls. Surprisingly, they found that methylation was lower in children of holocaust survivors than controls. So, the gene was marked for reduced expression in the victims, and increased expression in their children.

How these differences in expression impact the victim’s and their children’s psyche, remains to be worked out. Do trauma victim’s brain cells produce less FKBP5 protein, and therefore have more sensitive stress systems? Do victim’s children have too much FKBP5 that disrupts some necessary balance? These tentative and speculative questions will require more research. But these results open a new path towards treating PTSD, and illuminate the depth of trauma’s impact, reaching down to our genes and through the years.

epigen_ptsd-wm
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Written by Eric Harvey.

Image by Leslee Lazar

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This post was made in collaboration with Psychology in Action

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References:

Yehuda, R., Schmeidler, J., Wainberg, M., Binder-Brynes, K., & Duvdevani, T. (1998). Vulnerability to posttraumatic stress disorder in adult offspring of Holocaust survivors. American Journal of Psychiatry.

Yehuda, R., Daskalakis, N. P., Bierer, L. M., Bader, H. N., Klengel, T., Holsboer, F., & Binder, E. B. (2015). Holocaust exposure induced intergenerational effects on FKBP5 methylation. Biological psychiatry.

Eric Harvey

Eric Harvey

Eric is a 3rd year graduate student studying epigenetics of memory and drug abuse. Before graduate school he served in the army for 8 years. His favorite food is ramen, his least favorite food is omelettes, and he thinks Chris Farley was the best actor to come out of Saturday Night Live.
Eric Harvey

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Eric Harvey

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Eric is a 3rd year graduate student studying epigenetics of memory and drug abuse. Before graduate school he served in the army for 8 years. His favorite food is ramen, his least favorite food is omelettes, and he thinks Chris Farley was the best actor to come out of Saturday Night Live.

One Comment

  1. “Remarkably, a lifetime after the trauma, victims, and even their children, bore marks on their DNA. The researchers found that methylation was greater in holocaust survivors than the controls. Surprisingly, they found that methylation was lower in children of holocaust survivors than controls. So, the gene was marked for reduced expression in the victims, and increased expression in their children.”

    Sorry, I am very confused.

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